Blindness is the medical condition of lacking visual perception. As many as tens of millions of people, which account for 0.2% to 0.5% of the population of the world, are affected by blindness, and suffer from great losses in personal, social and economical respects. Retinal glaucoma or optic neuropathy is one of the leading causes of blindness worldwide. Glaucoma is the most common progressive optic neuropathy, leading to irreversible blindness. The global prevalence of glaucoma for people over 40 is as high as about 2% to 3%. Globally, there were an estimated 60 million people with glaucoma in 2010. The prevalence of glaucoma is expected to increase to 80 million by 2020 (Quigley H A and Broman A T, Br J Ophthalmol 2006; 90: 262-267). The prevalence of glaucoma in the socially active middle-aged generation is 2% to 3%, and it is expected that the number of patients will greatly increase as the population ages, which will become a social and economic burden. Currently, reduction of intraocular pressure is the only method that is clinically applied for glaucoma treatment, but it is known that a significant proportion of glaucoma patients still progress to blindness. It is known that reduction of intraocular pressure is a conservative method capable of merely inhibiting glaucoma progression, and treatment of the underlying glaucoma is impossible.
Meanwhile, optic neuropathy generally describes optic nerve abnormalities caused by different factors, and includes optic neuritis, ischemic optic neuropathy, toxic or deficiency optic neuropathy, hereditary optic neuropathy, optic atrophy, etc. Among them, the diseases caused by optic nerve degeneration and damage can be helped by stem cell therapy.
Specifically, glaucoma is caused by degeneration and loss of retinal ganglion cells (RGCs). After passing through the eye, light is converted to electric signals in photoreceptor cells, and retinal ganglion cells transmit these electric signals to the central optic nerve of the brain.
On the other hand, stem cell/regenerative therapy may be the best therapy for glaucoma and optic neuropathy. A disease caused by degeneration and loss of a single cell type is a strong target of stem cell therapy. In particular, because the eye is very easily accessible for surgical manipulation, and various surgical procedures have been established, there are no difficulties in the application of stem cells to lesions, and the eye can be a model for the development of therapeutic drugs.
The goals of stem cell therapy in glaucoma and optic neuropathy are 1) to replace degenerative and damaged RGCs with new RGCs (cell replacement therapy, neuro-regeneration), 2) to induce therapeutic effects of anti-inflammation, anti-cell death, neuroprotection, and vascular protection on degenerative and damaged RGCs as paracrine effects of stem cell therapy, and 3) to select and develop new drugs using stem cells for the treatment of glaucoma, for which direct therapeutic agents have not yet been developed. This therapy may lead to a personalized stem cell therapy using patient-derived pluripotent stem cells. Highly efficient production of retinal ganglion cells is essential in the development of therapeutic compositions or models for therapeutic drugs. In particular, there is a problem in that retinal ganglion cells degenerated or damaged by diseases cannot be prepared in vitro, and therefore, it is impossible to develop new drugs for glaucoma and optic neuropathy using normal or abnormal retinal ganglion cells. Therefore, if a large amount of retinal ganglion cells are produced from stem cells, it is possible to create disease models for retinal ganglion cell-associated diseases such as glaucoma and optic neuropathy, and therefore, drugs for the diseases can be easily developed. Especially, production of RGCs differentiated from patient-derived induced pluripotent stem cells (iPSC-RGCs) makes it possible to develop new drugs capable of preventing and inhibiting optic nerve degeneration. In addition, the present inventors disclosed a method of differentiating retinal cells from stem cells in the previous patents (Korean Patent NO. 10-1268741 (2013 May 22) and WO2011/043591 (2011 Apr. 14)). However, according to the methods disclosed in the above documents, only about 6% of retinal progenitor cells are differentiated into retinal ganglion cells. Accordingly, there is still a need to develop a differentiation method capable of maximizing differentiation into retinal ganglion cells.